Synthesis of 3-azabicyclo[3.1.0]hexanes by insertion of cyclopropylmagnesium carbenoids into an intramolecular C–H bond adjacent to a nitrogen atom

• Published in: Tetrahedron 2015-09, Vol.71 (35), p.5952-5958
• Main Authors: Kimura, Tsutomu, Wada, Natsumi, Tsuru, Takahiro, Sampei, Taro, Satoh, Tsuyoshi
• Format: Article
• Language: English
• Subjects: 1,5-C–H Insertion; 1-Chlorocyclopropyl p-tolyl sulfoxide; 3-Azabicyclo[3.1.0]hexane; Chiral auxiliary; Cyclopropylmagnesium carbenoid; Sulfoxide/magnesium exchange
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.02.059

A variety of 3-azabicylo[3.1.0]hexanes were synthesized via 1,5-C–H insertion of cyclopropylmagnesium carbenoids as a key step. 1-Chlorocyclopropyl p-tolyl sulfoxides with an N,N-disubstituted aminomethyl group on the cyclopropane ring were prepared from dichloromethyl p-tolyl sulfoxide, α,β-unsaturated carboxylic acid esters, primary amines, and alkyl halides. Treatment of the sulfoxides with i-PrMgCl generated cyclopropylmagnesium carbenoids, which were inserted into an intramolecular C–H bond adjacent to a nitrogen atom to give 3-azabicyclo[3.1.0]hexanes in yields of up to 94%. The reactivity of the C–H bond toward the insertion increased in the order of NCH3, NCH2CH3, NCH2Ph, and NCH(CH3)2. Optically active 3-azabicyclo[3.1.0]hexane was successfully synthesized using an S-chiral p-tolylsulfinyl group as a chiral auxiliary. [Display omitted]